A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer

Cancer Chemother Pharmacol. 2015 Oct;76(4):793-801. doi: 10.1007/s00280-015-2844-2. Epub 2015 Aug 22.


Purpose: Whether microdosing studies can be used to evaluate the human pharmacokinetics of new anticancer drugs remains unclear. The disposition of docetaxel in cancer patients is linear in terms of dose proportionality. We examined whether the pharmacokinetics of docetaxel in a clinically relevant therapeutic dose could be predicted from the pharmacokinetics of a microdose of docetaxel in Japanese patients with cancer.

Methods: A microdose of docetaxel (100 μg/patient) was given by 5-min intravenous infusion on day 1, followed by a therapeutic dose of docetaxel (60-75 mg m(-2)), given by 1-h intravenous infusion on day 8. Plasma docetaxel was analyzed by liquid chromatography-tandem mass spectrometry. A two-compartment pharmacokinetic model was used to calculate the area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf).

Results: Nine patients received both a microdose and therapeutic dose of docetaxel. The AUC0-inf after microdosing was 3640 ± 1150 ng h L(-1), while that after therapeutic dosing adjusted to 100 mg/patient was 2230 ± 757 µg h L(-1). The ratio of docetaxel clearance in therapeutic dose to that in microdose was 1.8 (P = 0.0041). Plasma α1-acid glycoprotein concentrations negatively correlated with docetaxel clearance at therapeutic dose, whereas the trend was weak at microdose.

Conclusion: Docetaxel clearance showed marginal nonlinearity between microdose and therapeutic dose, presumably because of saturation of plasma protein binding; however, the magnitude was within twofold, allowing practically acceptable extrapolation.

Keywords: Docetaxel; Microdose study; Pharmacokinetics; α1-acid glycoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Evaluation / methods*
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / analysis
  • Drugs, Investigational / pharmacokinetics*
  • Drugs, Investigational / therapeutic use
  • Female
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Japan
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Models, Biological*
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Orosomucoid / analysis
  • Taxoids / administration & dosage
  • Taxoids / blood
  • Taxoids / pharmacokinetics*
  • Taxoids / therapeutic use
  • Tubulin Modulators / administration & dosage
  • Tubulin Modulators / blood
  • Tubulin Modulators / pharmacokinetics*
  • Tubulin Modulators / therapeutic use


  • Antineoplastic Agents
  • Drugs, Investigational
  • Orosomucoid
  • Taxoids
  • Tubulin Modulators
  • Docetaxel